DESCRIPTION: (Applicant's Abstract) Regardless of the social class of the abuser, or the nature of the drug being abused, the abuse of drugs is embedded within social and developmental contexts. Furthermore, the manifestations of drug abuse are rarely limited to a single domain of disturbance and may be different in males and females. Similarly, the effects of drugs are influenced by, and in turn can alter the functioning of a number of neurochemical systems. Early exposure to drugs seems likely therefore to change subsequent development and drug vulnerability and the biobehavioral sequelae of drugs use is critical to understanding both the causes and effects of drug abuse. We propose therefore to study in male and female juvenile and adult bonnet macaques, the effects of THC and Methamphetamine, two drugs of significant and increasing abuse. We will examine the impact of early rearing conditions with known adverse consequences for behavioral and neurodevelopment which have been implicated in the biobehavioral response to these drugs. We also propose to study the effects of acute/chronic juvenile drug exposure as it affects subsequent biobehavioral development and vulnerability to drugs. Finally we will examine the short and long term biobehavioral impact of the comorbidity of adverse early rearing and juvenile drug exposure. Building on individually based operant data and Ethopharmacological approaches, we will use a new EthoOperant approach developed in our laboratory, which allows parallel evaluation of a) individual performance on video operants varying in difficulty and reinforcement schedule; and b) social/affective patterns, in groups of bonnet macaques. Computer-readable chips imbedded in the subjects' wrists, allow computer recording of individual operant performance, while standard observations used in our laboratory for 35 years, provide detailed measures of relevant behavior patterns. Neurobiological data to be obtained with the Etho-Operant material will employ CSF taps to examine a spectrum of peptidergic and monoaminergic functioning throughout the course of development.